ME/CFS for 18 years, recently diagnosed with D-Lactic acidosis as cause of symptoms and illness.

Go to page

Go to page

Senior Member

Dear All,
I have been ill with ME/CFS symptoms and even diagnosed with Fibromyalgia for 18 years but was recently diagnosed as D-Lactic acidosis.

I have recently been formally diagnosed with D-Lactic acidosis (without short bowel syndrome) in February 2017. The same symptoms were misunderstood or ignored by Doctors for so long because all other tests had been virtually normal.

I have been trying to make others aware of the similarity of ME/CFS to D-Lactic acidosis that Sheedy et al have written about and reported on after finding D-Lactic producing bacteria in CFS patients (report below).

D-La can be a very serious condition and I had neurological symptoms very similar to Jennifer Bria which would fluctuate from mild to extreme and had varying symptoms ranging from muscle pain and weakness, slurred speech, difficulty thinking to confusion, fatigue and breathing difficulty as though I had climbed a mountain without oxygen, hypoglycemia or dizziness along with abdominal symptoms, difficulty after eating carbohydrates and periods of sometimes severe abdominal pain and sickness.

I was diagnosed after noticing that my symptoms would temporarily stop after using antibiotics (metronidazole). I made an appointment with a Consultant Gastrointerologist who specializes in D-Lactic acidosis and was virtually diagnosed on the spot because I respond to antibiotics. In D-La Carbs and sugars cannot be properly metabolised and cause fluctuating levels of D-Lactic acid which can be found in spinal fluid causing neurological symptoms which act much like a poison.

Anyone with these symptoms or who respond to antibiotics can test themselves for D-La through total 0% abstention diet for all Carbohydrates and simple sugars. Results can take 64 plus hours and remaining on the diet for 4 to 6 weeks could be life changing as it was for me! Dr. Sarah Myhill has been advising the same diet for ME/CFS patients for years. The diet is difficult and symptoms will return if it is failed, even small amounts of Carbs and Sugars can cause the return of symptoms. The diet should only be considered after consulting a Doctor to make sure that it is appropriate.

Next SectionAbstract
Patients with chronic fatigue syndrome (CFS) are affected by symptoms of cognitive dysfunction and neurological impairment, the cause of which has yet to be elucidated. However, these symptoms are strikingly similar to those of patients presented with D-lactic acidosis. A significant increase of Gram positive facultative anaerobic faecal microorganisms in 108 CFS patients as compared to 177 control subjects (p<0.01) is presented in this report. The viable count of D-lactic acid producing Enterococcus and Streptococcus spp. in the faecal samples from the CFS group (3.5×107 cfu/L and 9.8×107 cfu/L respectively) were significantly higher than those for the control group (5.0×106 cfu/L and 8.9×104cfu/L respectively). Analysis of exometabolic profiles of Enterococcus faecalis and Streptococcus sanguinis, representatives of Enterococcus and Streptococcus spp. respectively, by NMR and HPLC showed that these organisms produced significantly more lactic acid (p<0.01) from 13C-labeled glucose, than the Gram negative Escherichia coli. Further, both E. faecalis and S. sanguinis secrete more D-lactic acid than E. coli. This study suggests a probable link between intestinal colonization of Gram positive facultative anaerobic D-lactic acid bacteria and symptom expressions in a subgroup of patients with CFS. Given the fact that this might explain not only neurocognitive dysfunction in CFS patients but also mitochondrial dysfunction, these findings may have important clinical implications.

You cannot avoid fruit sugars but lowering Carbs and Sugars should stop the production of D-Lactic acid and wide ranging neurological symptoms. The same diet may also help IBS.

I do not really use this site because i have been diagnosed and am getting treatment. I am just trying to get a message to as many people as possible who can try the diet for themselves. It is likely that at the very least a Subset have the same problem.

I have tried the ME/CFS Association. They have told me firmly that ME/CFS is caused by Viral infection and they have made no attempt to investigate. I am very suspect of their motivations and trying to get this out to as many people as possible. I was so unwell that i was close to suicide just at the point that I was diagnosed.

My belief is that there may be more than one form of Bacterial Overgrowth (acting as an infection through massive overgrowth possibly due to antibiotics through selection and resistance of certain bacteria) which can cause variants including milder GUT problems in IBS. Those with IBS can also use the same diet. It is an optimal diet for those with ME/CFS according to Dr. Sarah Myhill.

Senior Member

Hi, have some further information that may be of help from the ME Research. I am finding it hard to believe that the ME/CFS association are not prepared to investigate when there are so many as unwell as I was. Please pass this on to anyone who may benefit, especially those with undiagnosed neurological symptoms.

If you are a patient with ME/CFS or IBS, live in the Newcastle area, and are interested in taking part in this research, please contact Linda Tinkler for more information, at linda.tinkler@nhs.net.Irritable bowel syndrome (IBS) is a relatively common condition characterised by a number of symptoms affecting the digestive system, including stomach cramps, bloating, diarrhoea and constipation. The symptoms can be different between individuals, and are often triggered by stress or particular foods.

Interestingly, the prevalence of ME/CFS is estimated to be 35 times higher among people with IBS than in the rest of the population. And, conversely, there is also a high prevalence of IBS among people with ME/CFS.

But that’s not the only link between the two conditions. Both ME/CFS and IBS are often reported to occur after an infection, and they are also both associated with abnormal activation of the immune system, as indicated by raised levels of various cytokines and immune cells.

There is also evidence of changes to the gut microbiome in ME/CFS and IBS. The microbiome generally refers to the collection of around 100 trillion microorganisms, including bacteria, that live on or inside the human body. Many of these bacteria are beneficial to us and essential to our survival. In the gut, they live on the membranous lining, or mucosa, and break down our food and help protect us against infection. This whole area has become a hot topic of research in many diseases.

The similarities between ME/CFS and IBS suggest that the two conditions may be part of a spectrum of illness, with shared pathophysiological changes in response to infection. This is the fascinating idea that Prof. Yan Yiannakou and his team in Newcastle are planning to investigate in a new project recently awarded funding by ME Research UK.

Prof. Yiannakou suggests that, if the two conditions are linked in this way, then ‘patients with ME/CFS alone would have mucosal immune and microbiome changes that are similar to, though less pronounced, than patients with both ME/CFS and IBS’.

To explore this, the team will recruit four groups of individuals: 25 patients with ME/CFS alone, 25 with IBS alone, 25 with both ME/CFS and IBS, and 25 healthy control subjects. Following clinical assessment, blood samples will be collected to analyse a variety of markers of immune activation, while stool samples will be taken from which to measure changes in the faecal microbiome using DNA analysis.

In addition, in five individuals from each group, biopsies of the colon will be taken in order to analyse the mucosal immunology and microbiome more directly. This whole process is particularly challenging and involves invasive tests, so its feasibility and acceptability to patients need to be explored.

Although these are relatively small groups of patients, Prof. Yiannakou hopes that the results of this study will demonstrate that the techniques are achievable, and provide pilot data on which to base larger studies examining the links between the gut microbiome and immune system in ME/CFS and IBS.

Various gastrointestinal and neurological problems that are common in people with ME/CFS are surprisingly similar to the symptoms of “D-lactic acidosis”. This condition arises from bacterial fermentation of carbohydrates in the gastrointestinal tract, leading to increased lactic acid levels in the blood. Could there be an overgrowth of Gram-positive anaerobic lactic acid bacteria in the guts of ME/CFS patients too?

Scientists at the University of Melbourne in Australia examined the faeces of 108 ME/CFS patients and 177 healthy controls for the presence of the most common of the 500 different bacterial species that inhabit the human gut. Their paper in the journal In Vivo reported significantly increased levels of aerobic Gram-positive intestinal bacteria in the ME/CFS group than the controls, particularly Enterococcus and Streptococcus species which are the most common aerobic bacteria in humans. Moreover, the organisms found in the patients produced significantly more lactic acid than those from the healthy subjects (p<0.01), indicating that acidosis was at least a possibility in ME/CFS. The researchers postulate that increased colonisation by Enterococcus and Streptococcus could heighten intestinal permeability, assisting the absorption of D -lactic acid into the bloodstream. Increased gut permeability might also aid the release of endotoxins from the bacteria themselves, leading to inflammation, immune activation and oxidative stress, which are prominent features in a large subset of ME/CFS patients.

While the cause of the increased colonisation remains unclear, the researchers point out that eradication of all bacteria is not the answer; indigenous bowel microflora have both positive and negative impacts on health, and the balance of “good” to “bad” bacteria is important. And their next experimental step is to measure D- and L-lactic acid accumulation in the biofluids of ME/CFS patients to confirm whether D-lactic acidosis really is a factor. If so, existing interventions, such as short-course antibiotics, alkalinising agents, a low carbohydrate diet or dietary glucose restriction might prove to be useful.

Senior Member

I firmly believe I have this also - I respond to herbal antibiotics very well. I've mentioned it to my go who basically laughed and said only people in near death have acidosis... how can I go about getting tested in the UK? Do you know?

Senior Member

Hi, your Doctor is an idiot! None of them are trained to recognize D-La, which is why it took 18 years for me with extremes of illness. Even if not D-La there are other forms of Bacterial Overgrowth which can cause Fatigue and other CFS like symptoms. Bacterial Overgrowth is far more serious than it sounds and a poor prognosis of health.

If you have things like fatigue, dizziness, periods of difficulty thinking or breathing difficulty, muscle pain and or weakness or slurred speech (it can cause a host of different neurological problems and may be different from one person to another with fluctuating symptoms which can be acute, lessen or stop altogether at times. I also had periods of hypoglycemia, also fully diagnosed, caused by the Bacterial Overgrowth competing for my food. Hypoglycemia has also been reported by many CFS/ME).

Your Doctor is one of the reasons that these problems have remained undiagnosed for so long, he obviously does not have a clue or sufficient imagination to join the dots. I had to make my own diagnosis after 3 years of making my own investigations. Fortunately I was supported by a good Doctor who let me make my own appointments with consultant Gastroenterologists. You need to find a D-Lactic consultant or Gastroenterologist to investigate either D-La or Bacterial Overgrowth if you have GUT symptoms.

I have sent evidence below (Dr. Luke White; D-La more prevalent than we think) that anyone with Bacterial Overgrowth which causes Gastrointestinal symptoms is at risk of D-La. Many CFS/ME have IBS which may also be caused by Bacterial Overgrowth which is a common cause of Fatigue, Muscle symptoms and Diarrhea or Constipation (you can have more than one form of Bacterial Overgrowth and some Bacterial can live off Hydrogen and produce Methane which can cause Constipation and poor Motility which can result in D-La in a form of self perpetuating negative feedback loop. Although there are many causes of D-La including Diabetes which can also paradoxically be a product of Carbohydrates and Sugars! The whole loop may be caused by Carbs and Sugars and overuse of Antibiotics in Medicine and Agriculture). Poor motility alone can cause D-La!

D-La is supposed to be a rare condition associated with short bowel syndrome. I believe that it is not rare, but rarely tested for because of the belief that it is rare and only Blood Gasses during exaccerbations will show D-Lactic acidosis. Blood Gasses are probably never carried out for ME/CFS because it is misunderstood to be a psychological condition (blame Wessley). This has led to stagnation of investigations or understanding.

Dr. Luke White (below) believes that anyone suffering from Bacterial Overgrowth is at risk of D-La. Many ME/CFS have these symptoms. Join the dots....................

Carol Rees Parrish, M.S., R.D., Series Editor 26 PRACTICAL GASTROENTEROLOGY • SEPTEMBER 2015 NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #145 Luke White, D.O. Department of Critical Care Medicine, Memorial Hospital, South Bend, IN D-Lactic Acidosis: More Prevalent Than We Think? Luke White D-lactate acidosis, in which the D-isomer of lactate accumulates, may be more prevalent than once thought. This uncommon disorder has been reported in the setting of short bowel syndrome, and in particular, with high carbohydrate diets in children. Mental status changes and gait instability, the classic symptoms of D-lactate buildup, may not immediately lead the clinician to consider this uncommon disorder. The purpose of this article is to present information about D-lactate that will increase the readers’ level of vigilance for this disorder, which affects a broader group of patients than initially thought. REPRESENTATIVE CASE A 60 year old male presented to the emergency department after being referred by his primary care physician for evaluation of ataxia and slurred speech.1 These symptoms had waxed and waned over the course of five months. He had undergone an MRI previously that showed only chronic small vessel disease; a CT of the head performed on the day of admission revealed similar findings. Eight months prior to admission, the patient had suffered a small bowel volvulus necessitating resection of 420cm of necrotic jejunum and ileum. He also suffered from end-stage renal disease due to longstanding diabetes mellitus (DM) and hypertension, necessitating hemodialysis 3 times /week. Within hours after admission the patient became unresponsive and was intubated. He was found to have a severe metabolic acidosis with a pH of 7.02 and an anion gap of 26. Lactate and blood urea nitrogen levels were normal. No osmolar gap was present and a toxicology screen was negative. Hemodialysis was performed and the patient regained normal neurologic status. He was quickly extubated. D-Lactate, the dextrorotary isomer of lactate, was found to be markedly elevated on a blood specimen sent prior to dialysis. He recovered and was discharged with antibiotic therapy and counseling on dietary modifications. He was noncompliant with his recommended diet and was subsequently admitted multiple times with similar symptoms necessitating multiple intubations. These admissions usually (continued on page 28) 28 PRACTICAL GASTROENTEROLOGY • SEPTEMBER 2015 NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #145 D-Lactic Acidosis: More Prevalent Than We Think? occurred after meals heavy in carbohydrates (CHO) and immediately prior to scheduled sessions of dialysis. Normal Human Metabolism Lactic acid, like many organic molecules, consists of two mirror-image isomers. L-lactate is produced by the human body and is the isomer tested for in common “lactate” assays. D-lactate, the mirror image of L-lactate, is produced in minute concentrations in human metabolism via the methylglyoxal pathway that converts acetone derivatives to glutathione.2 These concentrations are clinically insignificant in normal human metabolism. Clinical Presentation and Mechanism of Encephalopathy D-lactate toxicity generally occurs with serum D-lactate levels over 3 mmol/L3 and is associated with acidosis and a variably presenting encephalopathy. The clinical presentation of the patient with D-lactate toxicity is characterized by acidosis and encephalopathy in the context of the above risk factors. The encephalopathy of D-lactic acidosis is highly variable. Symptoms may include memory loss, fatigue, and personality changes or cerebellar symptoms such as ataxia or dysarthria. Severe cases may involve syncope, coma and respiratory failure, as occurred in the case described.1,4,5,6 Symptoms are similar in both humans and in ruminants, which suffer an analogous disease due to malabsorption and dehydration.2 The cerebellum appears to be most sensitive to elevated D-lactate levels; investigation of potential toxicity should include a careful exam of cerebellar function with speech, gait and balance testing. The mechanism for D-lactate encephalopathy remains unclear. D-lactate freely passes into the cerebral spinal fluid.7 Serum and urine levels do not always correlate to symptoms4 and healthy volunteers infused with D-lactate showed no signs of encephalopathy even when concentrations reached up to 6.7 mmol/L.8 It has been proposed that given these findings, D-lactate may be a proxy for other neurotoxic organic acids that have not yet been identified.3,5 Some cases of D-lactate encephalopathy appear related to thiamine deficiency.9,5,3,10 Several findings suggest that D-lactate may be a direct player in precipitating neurologic symptoms. L-lactate buildup and acidemia do not by themselves (continued from page 26) cause encephalopathy. D-lactate directly infused into the brain in animal models, however, impairs memory and reduces brain cell survival.6 Symptoms of congenital pyruvate deficiency are similar to those seen in D-lactate toxicity.11 D-lactate (and acidosis itself) impairs the action of pyruvate dehydrogenase (PDH), interfering with pyruvate metabolism and inhibiting utilization of L-lactate as a fuel in the brain. As cerebellar PDH is already reduced relative to the serum, a relatively low concentration of D-lactate may lead to clinical symptoms, even as serum levels of PDH remain adequate.6,3 At-Risk Populations D-lactate toxicity has been historically associated with patients suffering from short bowel syndrome (SBS). Ingestion, parenteral infusion via D-lactate containing fluids (such as Ringer’s lactate), peritoneal lavage, and impaired metabolism and excretion have all contributed to D-lactate toxicity in patients without SBS, though these causes are rare. It is likely that pathologic D-lactate buildup is under diagnosed; surveillance of 470 randomly selected hospital patients revealed detectable D-lactate levels in nearly 3 percent; less than two-thirds of these patients had a history of gastrointestinal surgery.4 Patients with SBS, particularly those with colon in continuity, but also those with small bowel bacterial overgrowth (SBBO), are at high risk for derangement of the balance of gut flora, as described below. These patients are most at risk when they suffer from the delivery of excess CHO to colonic bacteria and are unable to effectively metabolize and excrete the D-lactate produced.2,3,4,5 See Table 1 for at risk populations. Laboratory Testing The clinician should suspect D-lactate toxicity in the patient presenting with neurologic symptoms, a gap or non-gap acidosis, and risk factors for D-lactate overproduction or retention. Obtaining a D-lactate level may confirm an often difficult clinical diagnosis. D-lactate is not detected in standard clinical lactic acid assays and requires a specific request from the lab. Despite this, an elevated concentration of D-lactate in the plasma always causes acidosis and usually leads to an increased anion gap. However, the anion gap may be lower than one would expect with similar concentrations (continued on page 30) 30 PRACTICAL GASTROENTEROLOGY • SEPTEMBER 2015 NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #145 D-Lactic Acidosis: More Prevalent Than We Think? more than the “usual” amount of CHO to the colon such as SBS or roux en y gastric bypass, can lead to an increase in lactate production via fermentation. This may occur either due to increased transit of CHO to the colon, to SBBO, or both.12 The luminal pH in the normal proximal small bowel is between 5.5 to 7.0. It becomes progressively more alkalotic through the jejunum and ileum. The cecal luminal pH is somewhat more acidotic (6.2) than the terminal ileum (7.6), but again becomes more alkalotic through the colon.17 As more CHO is fermented into lactate, luminal acidity increases and pH decreases. This decreasing pH selects for an increase in acid-tolerant fermenting bacteria, leading to a vicious cycle of fermenter overgrowth and increasing lactate production. Lactobacilli quickly become the predominant organism in patients suffering from SBS with malabsorption.14 Some of this lactate is translocated into the systemic circulation. While L-lactate is metabolized fairly readily, the human’s limited capacity for D-lactate metabolism and excretion,17 reduction of D-lactate metabolism due to acidosis,2 or interconversion between lactate isomers by certain lactobacilli,15,16,2 can all contribute to increasing concentrations of D-lactate. Defects in CHO absorption via an anatomic or functional short gut are responsible for most cases of pathologic bacterial overproliferation. D-lactate toxicity has also been reported in patients with SBS after the administration of probiotics consisting of D-lactate producing species, overconsumption of D-lactate producing yoghurt, and with the use of antibiotics that allow Lactobacillus overproliferation.4,10,3,5,18 Other Sources of D-Lactate While bacterial production accounts for the vast majority of cases of D-lactate toxicity, other causes have been reported. D-lactate appears to be elevated in at least some cases of diabetic ketoacidosis.19,20 One metabolic fate of D-lactate is conversion to fatty acids, but this can happen only in the context of high insulin levels,12 which most patients with DM lack. D-lactate toxicity has also been reported with propylene glycol ingestion.21 Propylene glycol is a diluent used in the preparation of many liquid medications, such as lorazepam. While lactic acidosis is a well-known complication of propylene glycol toxicity, controlled infusion of propylene glycol causes dosedependent increases in D-lactate, even as L-lactate of L-lactate or may even be normal.12 A fraction of D-lactate is excreted with sodium or potassium in the urine, which may lead to a relative non-gap (or low strong ion difference) acidosis. A normal anion gap does not therefore definitively exclude D-lactic acidosis. Testing for D-lactate requires a targeted assay and usually will require the services of a reference laboratory. This author utilizes Mayo Laboratories (Mayo Medical Laboratories, Rochester MN. http:// www.mayomedicallaboratories.com). D-lactate can be measured easily in urine and plasma specimens. Given high levels of urinary D-lactate excretion, a urine specimen will be more sensitive for clinically significant D-lactate toxicity. The turnaround time between specimen receipt and result may be up to 8 days. Because of this, laboratory testing should be considered supportive of a clinical diagnosis; treatment should not be delayed if the suspicion for toxicity is high. Causes Bacterial Production and the Short Bowel Syndrome Bacteria are almost always the predominant generator of D-lactate in mammals. Normal human gut flora is governed by a complex and still incompletely understood balance of factors. Normal human flora consists predominantly of Bacteroides and Firmicutes species; other species make up approximately 10% of the remainder. Concentrations of bacteria progressively increase by orders of magnitude from the stomach and duodenum to the colon.13 Both isomers of lactate are produced by usual human colonic flora as they metabolize small amounts of CHO, protein, non-absorbable starches, and fiber. The principal source of D-lactate production in the human gut is due to Lactobacillus and Bifidobacteri species.2 E. coli, Klebsiella pneumoniae and Candida freundii also produce significant quantities of D-lactate while producing minimal amounts of L-lactate.14 Some lactobacillus species are able to catalyze one lactate isomer to the other.15,16,2 Much of this lactate is converted to short chain fatty acids, which play an important role in the nutrition and maintenance of the mucosal integrity of the colonic epithelium.15 The delicate interplay of the healthy gut microbiome ensures that metabolites are appropriately utilized or excreted. Exposure of the colonic flora to excess (CHO), particularly in those with malabsorption, that presents (continued from page 28) NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #145 PRACTICAL GASTROENTEROLOGY • SEPTEMBER 2015 31 D-Lactic Acidosis: More Prevalent Than We Think? (the only isomer measured in common lactate assays), decreases.22 D-lactate is sometimes directly administered via some formulations of Ringer’s lactate containing both isomers of lactate. One review associated administration of fluids containing D-lactate with worsened clinical outcomes.23 Peritoneal dialysate may also be a source of D-lactate.3,5 Sepsis, gut ischemia, and intestinal perforation have been associated with elevated levels of D-lactate. This is likely due both to increased production and translocation across the damaged intestinal mucosa.24,25,26 D-lactate has in fact been suggested as a sensitive and specific marker of mesenteric ischemia,26 though the lack of ready availability of a D-lactate assay in most institutions limits its utility in this respect. Metabolism and Excretion Not all patients with SBS suffer from D-lactate toxicity, even when their CHO ingestion is unrestricted. Impaired D-lactate metabolism superimposed on excess production likely plays a significant role in most cases of toxicity.5,27 Accumulation of D-lactate in the circulation is abnormal. While early studies suggested that humans could not metabolize D-lactate, a certain quantity of D-lactate can in fact be metabolized into pyruvate via D-2 hydroxy acid dehydrogenase (D-2 HDH).5 Unlike L-lactate, which is efficiently metabolized, the metabolism of D-lactate is relatively slow and limited to a relatively small amount.17 D-2 HDH is found principally in the kidney and liver; impairment of these organs may lead to reduced D-lactate metabolism. Acidemia itself also impairs D-lactate metabolism due to a decrease in PDH activity, potentially leading to a loss of homeostasis should lactate levels accumulate enough to cause significant acidosis.3 Low levels of insulin may promote the buildup of D-lactate. Insulin inhibits the conversion of triglycerides to fatty acids, increasing the amount of organic acids, including D-lactate, that are metabolized. Thus, physiologic insulin release concurrent with CHO ingestion may have a protective effect in minimizing D-lactate toxicity.12 Even otherwise healthy patients with DM demonstrate elevated levels of serum and plasma D-lactate.28 Pyruvate acts as an intermediate product in D-lactate metabolism. Thiamine, a cofactor in pyruvate metabolism, may be deficient in patients suffering from malnutrition. Thiamine deficiency has been associated with lactic acidosis.9 Patients suffering from SBS, abnormal gut flora and/or malabsorption syndromes are at increased risk for thiamine deficiency. This deficiency, when paired with the elevated lactate production from abnormal gut flora, may lead to large amounts of excess lactate that cannot be effectively metabolized. The kidneys excrete a significant amount of D-lactate; the proportion excreted increases with increasing plasma concentrations.19 Limited metabolic potential makes renal excretion an important vehicle for elimination in cases of pathologic D-lactate production. While moderately decreased renal function does not seem to significantly reduce excretion,19 severe renal impairment, as in the case of patients dependent on hemodialysis, may lead to catastrophic levels of D-lactate.1 Treatment and Prevention D-lactate is the product of a substrate (usually CHO), produced largely by fermentative bacteria, which is then ultimately metabolized or excreted. D-lactate toxicity generally arises from excess substrate along with some catalyst for production, from impaired metabolism, excretion, or both.1,12 Effective prevention and treatment entails targeting each of these pathways. The mainstays of treatment are CHO restriction, hydration, cautious use of probiotics, and avoidance of SBBO (see Table 2). Table 1.Conditions Increasing the Risk of D-Lactate Toxicity High Risk Short Bowel Syndrome Roux-en-y gastric bypass Antibiotic or probiotic overuse Comorbid Conditions that may Increase Risk Thiamine deficiency Renal failure Diabetes Mellitus Propylene glycol ingestion 32 PRACTICAL GASTROENTEROLOGY • SEPTEMBER 2015 NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #145 D-Lactic Acidosis: More Prevalent Than We Think? NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #145 does not increase D-lactate levels, though it may reduce excretion as other organic acids compete with D-lactate for tubular excretion.7 Antimicrobial Strategies SBBO is responsible for most cases of D-lactate toxicity; prevention of this overgrowth is important.31 Antibiotic therapy (see Table 3) may increase or reduce D-lactate production, depending on the gut flora selected for. Trimethoprim-sulfamethoxazole (TMPSMX), doxycycline, and neomycin, for example, have each been associated with episodes of D-lactate encephalopathy.7,18,32 Each of these antibiotics has also been used in the *treatment* of SBBO.1,14,31 Likewise, metronidazole has been used successfully.30,16 but some lactobacilli in cases of D-lactate toxicity have exhibited metronidazole resistance.32 Rifaximin is increasingly used in the treatment of SBS with SBBO.31,33 Though lactobacilli can grow even at high intraluminal concentrations of rifaximin,34 to date no cases of D-lactate encephalopathy definitively associated with rifaximin use have been reported. A four-year study of fecal bacteria, lactate production, and resistance patterns in patients suffering SBS demonstrated poor results when attempting to treat D-lactate toxicity with antibiotic therapy; neomycin and oral vancomycin were successful in reducing certain lactobacillus isolates, but did not affect symptomatic resolution.14 A patient suffering from multiple episodes of D-lactic acidosis after TMP-SMX and doxycycline use suffered no episodes when taking ciprofloxacin, and cultured lactobacilli demonstrated ciprofloxacin sensitivity.32 Amoxicillin has been used due to its effective coverage of lactobacilli and high intraluminal gut concentration, but did not prevent recurrence when taken chronically.1 Antimicrobial therapy should be selected with caution in patients at risk for SBBO as certain antibiotics may select for lactate-producing gut flora. While it is reasonable to treat acute episodes of D-lactate toxicity with antibiotic therapy targeting Lactobacillus species, chronic preventive antibiotic therapy has not demonstrated consistent effect. In the patient suffering from recurrent episodes of D-lactate encephalopathy, fecal culture and sensitivities should be considered to ensure appropriately targeted therapy. Given the complexity of the healthy gut milieu, no single antibiotic regimen is likely to yield satisfactory results on its own. Diet Patients with SBS who are at risk for SBBO should be encouraged to limit simple CHO intake (cakes, cookies, pie, candies, etc.) as well as sugar alcohols (sorbitol, mannitol, xylitol, etc.), fructose and other highly osmolar, fermentable compounds and excess fiber.29,30 CHO should be complex and modest in quantity (16), with small and frequent meals to avoid exposure of the gut flora to large, poorly absorbed boluses of CHO. It has also been suggested that fermented foods, such as yoghurt, sauerkraut and pickles be avoided given high preexisting concentrations of D-lactate.3 In the patient with D-lactic encephalopathy, temporary cessation of all enteric feeding is reasonable. Elimination of substrate to the gut should prevent bacterial production. Fasting has been associated with rapid improvement in D-lactate associated encephalopathy.7,5 Concomitant parenteral nutrition (continued on page 43) Table 2. Treatment Options Substrate Reduction • Low simple CHO diet • Fructose and sugar alcohol avoidance • Temporarily remove all enteral substrates (oral/enteral feedings) o Parenteral nutrition if needed in severe cases • Adequate hydration (avoid Ringer’s Lactate) • Caution when using probiotics consisting of D-lactate producing species Reduced Production/Increased Excretion: • Antibiotic therapy for small intestinal bacterial overgrowth (see Table 3) • Thiamine repletion • Parenteral bicarbonate • Hemodialysis in severe cases NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #145 D-Lactic Acidosis: More Prevalent Than We Think? PRACTICAL GASTROENTEROLOGY • SEPTEMBER 2015 43 NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #145 Enhancement of Metabolism and Excretion Only a minority of patients who neglect dietary interventions will develop D-lactate toxicity, even if they are actively suffering from SBBO. One study of eleven patients with SBS and no neurologic symptoms demonstrated D-lactate overproduction in most fecal samples, but none in the urine.27 Symptoms should trigger a search for causes of impaired metabolism and excretion. Thiamine deficiency may both result from malnutrition and poor absorption, and contribute to reduced clearance of D-lactate due to impaired pyruvate metabolism.9 The cerebellum is particularly sensitive to thiamine deficiency.11 In some instances of encephalopathy associated with excess D-lactate, thiamine supplementation alone has led to symptomatic resolution.11,35 It is reasonable to supplement the patient suffering from neurologic symptoms with thiamine,9,5,3,10 particularly as this same set of patients is also at high risk for Wernicke’s Encephalopathy, which may present with similar neurologic findings. We recommend aggressive treatment, supplementing all patients with neurologic symptoms at risk for thiamine deficiency with 500mg parenterally three times daily for 1-2 days and then 100mg orally or parentally indefinitely thereafter. A significant proportion of D-lactate that accumulates in the serum is excreted in the urine.19 Impaired excretion can lead to D-lactate buildup. Maintenance of euvolemia is important in the prevention of D-lactate toxicity; aggressive hydration is crucial in its treatment. SBS is associated with dehydration, particularly in the case of malabsorption due to poor dietary adherence;29 consequently, patients suffering from SBBO may also suffer from renal hypoperfusion and reduced excretion of D-lactate. Of note, fluids such as Ringer’s lactate with racemic mixtures of lactate should be avoided.23 Hemodialysis effectively clears both isomers of lactate and has been successful in treating episodes of severe D-lactate toxicity.1,21,36 Anuric or oliguric patients already undergoing dialysis who suffer (continued from page 32) Table 3. Antibiotic Therapy No duration of therapy has been established but treatment should be short (e.g. 7-14 days) and limited to symptomatic resolution. Medication Rifaximin Amoxicillin Vancomycin (oral) Metronidazol Ciprofloxacin Neomycin* Trimethoprim-Sulfamethoxazole* Adult Dose 550mg 500mg 125-500mg 500mg 500mg 500mg 1 double strength tablet Daily Frequency 2-3 x 2 x 1-4 x 3 x 2 x 2 x 2 x *Note that these antibiotics have also been reported to provoke D-lactic acidosis 44 PRACTICAL GASTROENTEROLOGY • SEPTEMBER 2015 NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #145 D-Lactic Acidosis: More Prevalent Than We Think? recurrent episodes of D-lactate toxicity may benefit from longer or more frequent hemodialysis sessions to promote clearance, as they have no other means of excretion. Patients with D-lactate toxicity already undergoing peritoneal dialysis should be considered for hemodialysis given the presence of D-lactate in peritoneal dialysate.3,5 Other Proposed Treatments Bicarbonate has been given parenterally in the treatment of D-lactic acidosis.2,1,5 This may enhance D-lactate metabolism, as the responsible enzyme is impaired by acidosis. Notably, this is in contrast to recommendations that undifferentiated lactic acidosis (which is usually principally L-lactate) not be treated with bicarbonate.37 One case report reported symptomatic resolution with oral and intravenous bicarbonate administration.5 Bicarbonate has also been successful in the treatment of drunken lamb syndrome, an analogous process in ruminants, when given in conjunction with parenteral amoxicillin.38 Growth of lactate-producing fermentative bacteria both promotes, and is enhanced by, intraluminal acidosis. Antacids have thus been proposed3 as a potential treatment, but given the association of acid suppressive therapy with SBBO and increased intestinal transit time,33 they should be used with caution, if at all. D-lactate levels in otherwise healthy patients with DM can be elevated,28 possibly due to insulin deficiency or resistance. Insulin has been suggested as a potential therapy for severe D-lactic acidosis on the principle that it may inhibit lipolysis and thus promote increased metabolism of D-lactate.12 This has yet to be widely evaluated; at present it seems prudent to simply pursue usual treatment for hyperglycemia. SUMMARY D-lactate toxicity remains an uncommon, but likely under recognized syndrome. It occurs principally in patients with SBS who suffer acute processes that impair the limited human capacity to metabolize and excrete D-lactate, but may be missed in other disease processes due to the wide variability in symptoms and delay in obtaining confirmatory testing. Wider recognition of the syndrome and careful monitoring of those at risk for it, paired with a multidisciplinary approach to encourage compliance with dietary recommendations, will help to prevent and reduce its incidence even further. References 1. Htyte N, White L, Sandhu G, et al. An extreme and lifethreatening case of recurrent D-lactate encephalopathy. Nephrol Dial Transplant. 2011;26(4):1432-5. 2. Ewaschuk JB, Naylor JM, Zello GA. D-lactate in human and ruminant metabolism. J Nutr. 2005;135(7):1619-25. 3. Petersen C. D-lactic acidosis. Nutr Clin Pract. 2005;20(6):634- 45. 4. Rehman A, Badger C, Patel, N, et al. Brain fogginess, gas, bloating and distension: a link between SIBO, probiotics and metabolic acidosis. Poster. Presented (DDW 2014, Chicago, IL). Gastroenterology 2014;146(5):S850-1. 5. Uribarri J, Oh MS, Carroll HJ. D-lactic acidosis A review of clinical presentation, biochemical features, and pathophysiologic mechanisms. Medicine (Baltimore). 1998;77(2):73-82. 6. Gibbs ME, Hertz L. Inhibition of astrocytic energy metabolism by D-lactate exposure impairs memory. Neurochem Int. 2008;52(6):1012-8. 7. Karton M, Rettmer RL, Lipkin EW. Effect of parenteral nutrition and enteral feeding on D-lactic acidosis in a patient with short bowel. JPEN J Parenter Enteral Nutr. 1987;11(6):586-9. 8. Oh MS, Uribarri J, Alveranga D, et al. Metabolic utilization and renal handling of D-lactate in men. Metabolism. 1985;34(7):621-5. 9. Adeva-Andany M, López-Ojén M, Funcasta-Calderón R, et al. Comprehensive review on lactate metabolism in human health. Mitochondrion. 2014;17:76-100. 10. Ku WH, Lau DC, Huen KF. Probiotics provoked D-lactic acidosis in short bowel syndrome: Case report and literature review. Hong Kong J. Paediatr. 2006;11:246-254 11. Vella A, Farrugia G. D-lactic acidosis: pathologic consequence of saprophytism. Mayo Clin Proc. 1998;73(5):451-6. 12. Halperin ML, Kamel KS. D-lactic acidosis: turning sugar into acids in the gastrointestinal tract. Kidney Int. 1996;49(1):1-8 13. Schippa S, Conte MP. Dysbiotic events in gut microbiota: impact on human health. Nutrients. 2014;6(12):5786-805. 14. Bongaerts GP, Tolboom JJ, Naber AH, et al. Role of bacteria in the pathogenesis of short bowel syndrome-associated D-lactic acidemia. Microb Pathog. 1997;22(5):285-93. 15. Wong JM, de Souza R, Kendall CW, et al. Colonic health: fermentation and short chain fatty acids. J Clin Gastroenterol. 2006;40(3):235-43 16. Hove H, Mortensen PB. Colonic lactate metabolism and D-lactic acidosis. Dig Dis Sci. 1995;40(2):320-30. 17. Nugent SG, Kumar D, Rampton DS, et al. Intestinal luminal pH in inflammatory bowel disease: possible determinants and implications for therapy with aminosalicylates and other drugs. Gut. 2001;48(4):571-7. 18. Flourie B, Messing B, Bismuth E, et al. [D-lactic acidosis and encephalopathy in short-bowel syndrome occurring during antibiotic treatment]. Gastroenterol Clin Biol. 1990;14(6-7):596-8. 19. Bo J, Li W, Chen Z, et al. D-lactate: a novel contributor to metabolic acidosis and high anion gap in diabetic ketoacidosis. Clin Chem. 2013;59(9):1406-7. 20. Lu J, Zello GA, Randell E, et al. Closing the anion gap: contribution of D-lactate to diabetic ketoacidosis. Clin Chim Acta. 2011;412(3-4):286-91. 21. Jorens PG, Demey HE, Schepens PJ, et al. Unusual D-lactic acid acidosis from propylene glycol metabolism in overdose. J Toxicol Clin Toxicol. 2004;42(2):163-9. NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #145 PRACTICAL GASTROENTEROLOGY • SEPTEMBER 2015 45 D-Lactic

Senior Member

Thank you so much for your reply.
I have awful gut problems - my m.e started with gut symptoms. It wasn't until I started taking a probiotic called Symprove (a liquid based probiotic full of acidophilus and enterococcus feacium) that the neuro symptoms started (horrible!). Since taking this I have been unable to get it under control fully. Every month I have a bad episode and have to have zero carbs plus oregano oil for 2-3 days - any longer and I become so weak with no carbs. I know I have a dysbiosis due to my horrible gut symptoms (so bloated, nausea ect ect). I can go back to my Dr but he has already said he won't refer me to local gastro''s. He says they will laugh me out of the room. It makes me so sad as I know 100% my gut is seriously implicated in my illness. No one will help me though. And I have no idea where to turn to...

I have a zero sugar diet. No wheat. No fruit. I have followed this for years. I take l lacto gg probiotic on and off as others make me feel so poorly!

Senior Member

Hi Vicki,
I forgot, you are quite correct Herbal antibiotics may work or help. Garlic and Antibacterials can also be helpful. Dr. Myhill also uses Herbal Antibiotics/Antibacterials for Bacterial Overgrowth (she treats ME/CFS with a 'stone age diet'. She is one of the most intelligent Doctors that I have ever encountered and put her information up her website for free. She has also started an abuse in ME/CFS/Contact your MP.).

The Consultant Gastroenterologist who I saw for Bacterial Overgrowth before being diagnosed with D-La uses Antibacterials with Antibiotics.

For some Antibiotics can cure Bacterial Overgrowth, but it can also remain without permanent cure and Antibiotics can be used cyclically once a month although this can lead to antibiotic resistance. But it is better to use the exclusion diet and only use Antibiotics if you have an exaccerbation (caused by high level of D-Lactic acid and the cause of the worst symptoms. D-La can cause varying levels of illness and can also be fatal. It can cause from mild to multiple systemic neurological problems including tachyarrhythmias).

In trying to eradicate Bacterial Overgrowth, you may also damage good Bacteria which may lead to reducing good Bacterial colonies. Research is badly needed to properly understand the many thousands of symbiotic bacterial colonies and related policing by the immune system. The exclusion diet is the hardest but best option.

However, the last article talks about type A and B lactic acidosis and states that thiamine is only beneficial for type B, whereas the description of type A lactic acidosis sounds like what happens with ME/CFS.

Lactic acidosis, the most common kind of metabolic acidosis, is characterized by reduced blood pH (usually <7.25) in association with marked increase in blood lactate (usually >5.0 mmol/L). Lactic acidosis has many possible causes but two broad etiological classes have been defined: type A (hypoxic) lactic acidosis and type B (non-hypoxic) lactic acidosis.

Of the two, type A lactic acidosis, i.e. lactic acidosis arising from reduced tissue perfusion and/or severe hypoxemia, is the more common. In the absence of an adequate oxygen supply, tissue cells must depend on less efficient anaerobic metabolism of glucose for its energy production, and this alternative metabolic pathway results in accumulation of lactic acid.

Deficiency of vitamin B1 (thiamine) is a very rare cause of type B lactic acidosis that is highlighted in two recently published papers. The mechanism of lactic acidosis in vitamin B1 deficiency is explained by the fact that thiamine is an essential co-factor for the enzyme pyruvate dehydrogenase that allows oxidation of pyruvate to acetyl CoA.

This is a key step in the process that allows energy production, in the form of ATP, from glucose oxidation. In the absence of thiamine this reaction cannot proceed and instead, pyruvate is converted to lactate. The resulting accumulation of lactate causes lactic acidosis.

However, so little research has been done on ME/CFS and nutrition in general, I would not just accept the statement that thiamine is only beneficial for type B lactic acidosis and by inference, not type A. Thiamine has improved my energy - people with ME/CFS have abnormal nutritional requirements.

Hi, yes I had extremes of post exertional malaise (this could vary from mild to extreme at different times). The symptoms also felt at times like infections or Flu at times. Jennifer Brea also describes her symptoms as infections, which resolve temporarily with antibiotics (Times interview).

I was bed ridden and also very unwell at times. Often repeated activity would lead to prolonged periods of bed rest. I could not recover from normal activity as I had before becoming unwell. I had very bad symptoms and was expecting to either die or to have to commit suicide because Doctors could not recognize the symptoms (I made my will expecting to die from the symptoms on a number of occasions).

I also had systemic pain (I now have to remember, as receiving treatment and much of this is only a bad memory). I had pin prick sensations during the worst illness when I would become confused or have difficulty thinking and was only diagnosed with D-La when I realized that my symptoms abated after using Antibiotics.

Sometimes I would have tacharrhymias or fast heartbeats after activity, at worst after pushing things with chest pain. Because I was told that there was nothing wrong with me I would repeatedly push things until I became very unwell. My memory was also badly affected and long term acidosis can lead to cellular damage especially to the brain where cells cannot be replaced and it is likely that this may lead to early dementia.

D-La and Bacterial Overgrowth needs urgent research. Bacterial Overgrowth alone can cause malabsorbtion of vitamins and autoimmune disease causing the immune system to attack its host cells. This is a complex problem.

Senior Member

Thank you so much for your reply.
I have awful gut problems - my m.e started with gut symptoms. It wasn't until I started taking a probiotic called Symprove (a liquid based probiotic full of acidophilus and enterococcus feacium) that the neuro symptoms started (horrible!). Since taking this I have been unable to get it under control fully. Every month I have a bad episode and have to have zero carbs plus oregano oil for 2-3 days - any longer and I become so weak with no carbs. I know I have a dysbiosis due to my horrible gut symptoms (so bloated, nausea ect ect). I can go back to my Dr but he has already said he won't refer me to local gastro''s. He says they will laugh me out of the room. It makes me so sad as I know 100% my gut is seriously implicated in my illness. No one will help me though. And I have no idea where to turn to...

I have a zero sugar diet. No wheat. No fruit. I have followed this for years. I take l lacto gg probiotic on and off as others make me feel so poorly!

Hi Vicki,
I was also bloated and would burp up/regurgitate food or feel sick. This is a symptom of Bacterial Overgrowth!

You should ask for another Doctor to assess you. You may need a Hydrogen or Methane test for the gasses produced by Bacterial Overgrowth which can be secondary to other underlying conditions including diabetes, poor motility or more severe illness. You could pay for an private appointment with Consultant Gastroenterologist Dr. Ray Shidrawi who also works for the NHS Homerton University Hospital. He can investigate and treat Bacterial Overgrowth and then you could be assessed for D-La after Bacterial Overgrowth confirmation.

Some probiotics have been implicated in increased D-Lactic production. Much of the research is divided on the efficacy of probiotics. I use non Lactic producing bacteria such as Bifidobacteria variants and Prebiotics but i am still experimenting. You may find the report below useful. I came across it while researching my own symnptoms (you can find the full report online). But probiotics/prebiotics have to be combined with 0% Carbohydrate and Simple Sugar diet (or the lowest possible).

I was going to sat that you must always check with your Doctor before starting any change to your diet. But it seems that you may get better advice from your cat (or if you do not own one somebody else's cat!. A low Carbohydrate diet can be dangerous in problems such as Glycogen Storage Disease).

Abstract
Synbiotics are combinations of probiotics and prebiotics that have recently been used in the context of various gastrointestinal diseases, including infectious enteritis, inflammatory bowel disease, and bowel obstruction. We encountered a patient with recurrent D-lactic acidosis who was treated successfully for long periods using synbiotics. The patient was diagnosed as having short bowel syndrome and had recurrent episodes of neurologic dysfunction due to D-lactic acidosis. In addition to fasting, the patient had been treated with antibiotics to eliminate D-lactate-producing bacteria. After the failure of antibiotic treatment, a stand-alone synbiotic treatment was started, specifically Bifidobacterium breve Yakult and Lactobacillus casei Shirota as probiotics, and galacto-oligosaccharide as a prebiotic. Serum D-lactate levels declined, and the patient has been recurrence-free for 3 years without dietary restriction. Synbiotics allowed the reduction in colonic absorption of D-lactate by both prevention of D-lactate-producing bacterial overgrowth and stimulation of intestinal motility, leading to remission of D-lactate acidosis.

Senior Member

I became so intolerant to Carbs that I would suffer reactive hpoglycemia and my stomach would at times not empty quickly overnight causing me to choke on inhaled food while sleeping during the night.

Rifaximin is used for both Bacterial Overgrowth and D-Lactic acidosis although there are many other useful antibiotics such as Metronidazole which is fast acting if you have developed neurological symptoms during exaccerbations of D-La.

Did you have any neurological symptoms?: difficulty thinking, slurred speech, systemic symptoms feeling like flu or infection like symptoms (muscle pain or weakness) without temperature, pin prick/pins and needles, breathing difficulty etc. or just Bacterial Overgrowth (which is known to cause hypoglycemia, fatigue, muscle pain, digestive problems and autoimmune symptoms)?

Not sure where L-Lactic acid fits in but Sheedy et al in their 2017 report believe that there are a number of other toxins as well as D-Lactic acid produced by the same Bacteria that produces D-Lactic acid in CFS/ME.

The only way that you could be tested for D-La is to have Blood Gas investigations during an exaccerbation after coming off rifaxamin.

No one fully understands the full underlying pathology in D-La. No one has properly mapped the different strains of bacteria or DNA or understands fully the interaction of symbiotic strains or what part each plays in digesting food or immune policing to maintain good symbiosis.

This is an unexplored continent. There is no map of healthy Gut symbiosis for comparative understanding.

Possibly a fecal transplant may work from a healthy donor, but these tend to fail due to underlying problems that have caused Bacterial Overgrowth in the first place.

Senior Member

Thank you so much Paul for your information. I'm taking all this back to my gp to see if I can be referred. I've tried for 2 days with no carb but i feel so weak because of it... I'm at a loss and I know I need professional assistance. Thanks again for your help and time, Vicki

Hi, yes I have to maintain the Diet for ever, unless the underlying cause can be identified and treated. I am making enquiries into fecal transplant/prebiotic, probiotic treatment with Bacteria that may help, but it may be the case that there is no cure only treatment because for some reason the Overgrowth causing D-La has not responded to antibiotics and I have become resistant to at least 4 antibiotics. The Diet is the only way that i can live normally without ME symptoms.

The condition is found mainly/supposedly in Short Bowel syndrome. My belief is that it has been grossly underestimated. I have D-La without Short Bowel syndrome or any structural abnormality. If I can have D-La, then anyone can have it. Dr. Luke Whit believes that D-La is 'more prevalent than we think' and that anyone with Bacterial Overgrowth is at risk of D-La. Bacterial Overgrowth and Gut symptoms have been found in many ME/CFS patients.